Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Laboratory of Dermatoimmunology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Biochem Biophys Res Commun. 2019 May 28;513(2):452-459. doi: 10.1016/j.bbrc.2019.03.185. Epub 2019 Apr 6.
Sleep deprivation affects the pathophysiology of immune-inflammatory skin diseases such as psoriasis. Increasing efforts are directed toward exploring potential mechanisms involving sleep deprivation and immune responses. However, studies focusing on the effects of different timing of sleep deprivation on skin inflammation are lacking. This study thus investigated the immunomodulatory effects of paradoxical sleep (PS) deprivation at different timing of psoriasiform process on skin inflammation in the psoriasis-like mouse model. Male adult C57BL/6 mice were divided into 5 groups (each n = 5): control group (CON), IMQ-S2 group [treating with 31.25 mg imiquimod (IMQ) per day for 5 days with 48 h of PS deprivation on the fourth and fifth day], S2-IMQ group (treating with 31.25 mg IMQ per day for 5 days with 48 h of PS deprivation on the first and second day), 31.25 group (treating with 31.25 mg IMQ per day for 5 days) and 62.5 group (treating with 62.5 mg IMQ per day for 5 days). Compared with IMQ-S2 group and 31.25 group, S2-IMQ group mice had significant increase of IL-17A mRNA level in skin lesions and lymph nodes, and more severe cutaneous inflammation. However, IMQ-S2 group had the highest IL-1β mRNA level in skin lesions and the highest IL-6 mRNA level in lymph nodes among the three groups. Results of flow cytometry showed that frequencies of γδT cell, IL-17A+γδT cell, dendritic cell (DC) and MHCⅡ+ DC in lymph nodes of S2-IMQ group were significantly higher than IMQ-S2 group and 31.25 group, so was the frequency of γδT cells in skin lesions. However, the frequency of DCs in skin lesions of S2-IMQ group was significantly lower than IMQ-S2 group. These data suggest that PS deprivation at the early stage rather than the late stage of psoriasiform process exacerbates the skin inflammation through modulation of the immune system, which may involve that IL-1β and IL-6 stimulated by PS deprivation in turn increasing IL-17 expression through activation and proliferation of γδT cells and DCs migration.
睡眠剥夺会影响免疫炎症性皮肤病（如银屑病）的病理生理学。目前越来越多的研究致力于探索与睡眠剥夺和免疫反应相关的潜在机制。然而，目前缺乏关于睡眠剥夺不同时间对皮肤炎症影响的研究。因此，本研究旨在探讨银屑病样小鼠模型中，在银屑病样过程的不同时间点进行反常睡眠（PS）剥夺对皮肤炎症的免疫调节作用。将成年雄性 C57BL/6 小鼠分为 5 组（每组 n=5）：对照组（CON）、IMQ-S2 组[每天用 31.25mg 咪喹莫特（IMQ）处理 5 天，第 4 天和第 5 天有 48 小时 PS 剥夺]、S2-IMQ 组（每天用 31.25mg IMQ 处理 5 天，第 1 天和第 2 天有 48 小时 PS 剥夺）、31.25 组（每天用 31.25mg IMQ 处理 5 天）和 62.5 组（每天用 62.5mg IMQ 处理 5 天）。与 IMQ-S2 组和 31.25 组相比，S2-IMQ 组小鼠皮肤损伤和淋巴结中 IL-17A mRNA 水平显著升高，皮肤炎症更严重。然而，IMQ-S2 组皮肤损伤中 IL-1β mRNA 水平最高，淋巴结中 IL-6 mRNA 水平最高。流式细胞术结果显示，S2-IMQ 组淋巴结中 γδT 细胞、IL-17A+γδT 细胞、树突状细胞（DC）和 MHCⅡ+DC 的频率明显高于 IMQ-S2 组和 31.25 组，皮肤损伤中 γδT 细胞的频率也明显高于 IMQ-S2 组。然而，S2-IMQ 组皮肤损伤中 DC 频率明显低于 IMQ-S2 组。这些数据表明，在银屑病样过程的早期而非晚期进行 PS 剥夺会通过调节免疫系统加重皮肤炎症，这可能涉及 PS 剥夺刺激的 IL-1β 和 IL-6 通过 γδT 细胞的激活和增殖以及 DC 的迁移来增加 IL-17 的表达。
